In the search for novel sterol demethylase inhibitors (DMIs), a series of 1,2,4-triazole derivatives containing oxime ether and cyclopropyl moieties were designed using the bioactive substructure combination assisted by virtual molecular docking. The above-mentioned target compounds were characterized using the ¹H NMR, ¹³C NMR, ¹⁹F NMR, and HR-MS spectra. The antifungal evaluation against Rhizoctonia solani (Rs), Fusarium graminearum (Fg), and Botrytis cinerea (Bc) indicated that most of the target compounds exhibited remarkable inhibitory activities against the above-mentioned tested fungi. Significantly, the compound 5k exhibited outstanding anti-Fg activity with an EC₅₀ value of 1.22 μg mL⁻¹in vitro, and a protective effect of 59.45% in vivo at 200 μg mL⁻¹. Further investigation revealed that compound 5k evidently inhibited Fg spore germination and caused some wrinkles and dents on the surface of mycelia. Molecular docking showed that compound 5k bound with the target protein FgCYP51 via coordination, hydrogen bonding and stacking interactions that were similar, but slightly different from the interactions of tebuconazole with FgCYP51. These research results suggested that the target compounds are valuable for the further structural optimization of novel triazole fungicides.